Skip to main content
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1982 Mar;13(3):375–378. doi: 10.1111/j.1365-2125.1982.tb01388.x

A simple pharmacokinetic method for separating the three acetylation phenotypes: a preliminary report.

E J Lee, L K Lee
PMCID: PMC1402120  PMID: 7059437

Abstract

1 Until recently, phenotyping the N-acetyltransferase enzyme had been restricted to distinguishing the slow acetylators from the rapid. Further separation of the heterozygous rapid phenotype from the homozygous rapid phenotype has only been possible by detailed pharmacokinetic studies using sulphadimidine and necessitating prolonged plasma sampling. 2 A simple method of deriving the basic pharmacokinetic parameters is presented. In this study of ten healthy volunteers, one urine sample and hourly plasma sampling over only 5 h enabled calculation of the total body (TBC) and metabolic clearances (MC) wih enough accuracy to distinguish the three (slow, intermediate and rapid) acetylator phenotypes. The spread of the distribution for the elimination rate constant was however too wide to enable their clear separation.

Full text

PDF

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bulovskaya L. N., Krupkin R. G., Bochina T. A., Shipkova A. A., Pavlova M. V. Acetylator phenotype in patients with breast cancer. Oncology. 1978;35(4):185–188. doi: 10.1159/000225282. [DOI] [PubMed] [Google Scholar]
  2. Chapron C. J., Blum M. R. Relationship of sulfamethazine disposition kinetics to acetylator phenotype in man. A preliminary study. J Clin Pharmacol. 1976 Jul;16(7):338–344. doi: 10.1002/j.1552-4604.1976.tb01530.x. [DOI] [PubMed] [Google Scholar]
  3. Chapron D. J., Kramer P. A., Mercik S. A. Kinetic discrimination of three sulfamethazine acetylation phenotypes. Clin Pharmacol Ther. 1980 Jan;27(1):104–113. doi: 10.1038/clpt.1980.16. [DOI] [PubMed] [Google Scholar]
  4. Das K. M., Eastwood M. A., McManus J. P., Sircus W. Adverse reactions during salicylazosulfapyridine therapy and the relation with drug metabolism and acetylator phenotype. N Engl J Med. 1973 Sep 6;289(10):491–495. doi: 10.1056/NEJM197309062891001. [DOI] [PubMed] [Google Scholar]
  5. Drayer D. E., Reidenberg M. M. Clinical consequences of polymorphic acetylation of basic drugs. Clin Pharmacol Ther. 1977 Sep;22(3):251–258. doi: 10.1002/cpt1977223251. [DOI] [PubMed] [Google Scholar]
  6. Ellard G. A., Gammon P. T. Acetylator phenotyping of tuberculosis patients using matrix isoniazid or sulphadimidine and its prognostic significance for treatment with several intermittent isoniazid-containing regimens. Br J Clin Pharmacol. 1977 Feb;4(1):5–14. doi: 10.1111/j.1365-2125.1977.tb00659.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Glowinski I. B., Radtke H. E., Weber W. W. Genetic variation in N-acetylation of carcinogenic arylamines by human and rabbit liver. Mol Pharmacol. 1978 Sep;14(5):940–949. [PubMed] [Google Scholar]
  8. Jounela A. J., Pasanen M., Mattila M. J. Acetylator phenotype and the antihypertensive response to hydralazine. Acta Med Scand. 1975 Apr;197(4):303–306. doi: 10.1111/j.0954-6820.1975.tb04922.x. [DOI] [PubMed] [Google Scholar]
  9. Lunde P. K., Frislid K., Hansteen V. Disease and acetylation polymorphism. Clin Pharmacokinet. 1977 May-Jun;2(3):182–197. doi: 10.2165/00003088-197702030-00003. [DOI] [PubMed] [Google Scholar]
  10. Mitchell J. R., Thorgeirsson U. P., Black M., Timbrell J. A., Snodgrass W. R., Potter W. Z., Jollow H. R., Keiser H. R. Increased incidence of isoniazid hepatitis in rapid acetylators: possible relation to hydranize metabolites. Clin Pharmacol Ther. 1975 Jul;18(1):70–79. doi: 10.1002/cpt197518170. [DOI] [PubMed] [Google Scholar]
  11. Nelson S. D., Mitchell J. R., Timbrell J. A., Snodgrass W. R., Corcoran G. B., 3rd Isoniazid and iproniazid: activation of metabolites to toxic intermediates in man and rat. Science. 1976 Sep 3;193(4256):901–903. doi: 10.1126/science.7838. [DOI] [PubMed] [Google Scholar]
  12. Olson W., Miceli J., Weber W. Dose-dependent changes in sulfamethazine kinetics in rapid and slow isoniazid acetylators. Clin Pharmacol Ther. 1978 Feb;23(2):204–211. doi: 10.1002/cpt1978232204. [DOI] [PubMed] [Google Scholar]
  13. Serdula M. K., Rhoads G. G. Frequency of systemic lupus erythematosus in different ethnic groups in Hawaii. Arthritis Rheum. 1979 Apr;22(4):328–333. doi: 10.1002/art.1780220403. [DOI] [PubMed] [Google Scholar]
  14. Vree T. B., O'Reilly W. J., Hekster Y. A., Damsma J. E., van der Kleijn E. Determination of the acetylator phenotype and pharmacokinetics of some sulphonamides in man. Clin Pharmacokinet. 1980 May-Jun;5(3):274–294. doi: 10.2165/00003088-198005030-00006. [DOI] [PubMed] [Google Scholar]
  15. du Souich P., McLean A. J., Stoeckel K., Ohlendorf D., Gibaldi M. Screening methods using sulfamethazine for determining acetylator phenotype. Clin Pharmacol Ther. 1979 Dec;26(6):757–765. doi: 10.1002/cpt1979266757. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES